The development of safe, efficient, and simple methods for selective incorporation of fluorine into organic compounds has become a very important area of technology. This is due to the fact that fluorine strategically positioned at sites of synthetic drugs and agrochemical products significantly modifies and enhances their biological activities. The conversion of the C--O to the C--F bond, which is referred to here as a deoxofluorination, represents a viable method to produce selectively fluorinated organic compounds, but the low yields and hazards associated with the current deoxofluorination reagents and processes severely limit the application of this technique.
The introduction of fluorine into medicinal and agrochemical products can profoundly alter their biological properties. Fluorine mimics hydrogen with respect to steric requirements and contributes to an alteration of the electronic properties of the molecule. Increased lipophilicity and oxidative and thermal stabilities have been observed in such fluorine-containing compounds.
In view of the importance of organofluorine compounds, efforts aimed at the development of simple, safe, and efficient methods for their synthesis have escalated in recent years. The conversion of the carbon-oxygen to the carbon-fluorine bond by nucleophilic fluorinating sources (deoxofluorination) represents one such technique which has been widely used for the selective introduction of fluorine into organic compounds. A list of the deoxofluorination methods practiced to date includes: nucleophilic substitution via the fluoride anion; phenylsulfur trifluoride; fluoroalkylamines; sulfur tetrafluoride; SeF.sub.4 ; WF.sub.6 ; difluorophosphoranes and the dialkylaminosulfur trifluorides (DAST). The most common reagent of this class is diethylaminosulfur trifluoride, Et-DAST or simply DAST.
Compounds containing the NSF.sub.3 moiety were first reported in the late 1960s; G. C. Demitras, R. A. Kent, and A. C. MacDiarmid, Chem. Ind. (London) (1964), p1712; G. C. Demitras and A. C. MacDiarmid, Inorg. Chem. (1967), 6, pp1903-1906 and early 1970s; S. P. Von Halasz and O. Glemser, Chem. Ber. (1971), 104, pp1247-1255, however, their use as deoxofluorination agents was not disclosed in these citations. It wasn't until the work of Markovskij et al.; L. N. Markovskij, V. E. Pashinnik, and A. V. Kirsanov, Synthesis, (1973), pp787-789 that the dialkylaminosulfur trifluoride compounds were first shown to be effective fluorinating agents for a wide range of organic substrates. Following this initial report, two patents; W. J. Middleton, U.S. Pat. No. 3,914,265 and W. J. Middleton, U.S. Pat. No. 3,976,691 and a publication; W. J. Middleton, J. Org. Chem. (1975), 40, pp574-578 appeared which fully disclosed the utility of these new compounds in deoxofluorination type reactions.
The analogous SF.sub.2 compounds were actually reported in the literature; the Middleton article immediately above and L. N. Markovskij, V. E. Pashinnik, A. V. Kirsanov, Zh. Org. Khim. (1975), 11(1) pp72-74 and in a patent; W. J. Middleton, U.S. Pat. No. 3,888,924. The SF.sub.2 compounds are also know to function as deoxofluorination agents.
The various SF.sub.3 compounds were first prepared through the reactions of SF.sub.4 with the corresponding trimethylsilylated amine, (Me).sub.3 SiNRR' in accordance with the literature set forth above, but have also been successfully made by the direct reaction of SF.sub.4 with the free amine, RR'NH, in the presence of an HF scavenger; L. N. Markovskij, V. E. Pashinnik, A. V. Kirsanov, USSR Patent 433136 (Application No. 1864289/234) or the sulfoxide of the amine, R.sub.2 NS(O)R', with concomitant formation of the sulfinic fluoride, R'S(O)F; L. N. Markovskij, V. E. Pashinnik, A. V. Kirsanov, Zh. Org. Khim. (1976), 12(5) pp973-974. Similarly, the previously known SF.sub.2 compounds have been prepared through the reaction of the corresponding SF.sub.3 compound, RR'NSF.sub.3, with either a second molecule of the trimethylsilylated amine, (Me).sub.3 SiNRR' in accordance with the above literature, or a molecule of a diaminosulfinate, R.sub.2 "NS(O)NR.sub.2 " in accordance with Markovshkij, et. al., immediately above.
The methods of preparation for trimethylsilylated imidazole derivatives are available in the literature; R. E. Wasylishen, G. S. Birdi, A. F. Janzen, Inorg. Chem. (1976), 15(12), pp3054-3056; A. F. Janzen, G. N. Lypka, R. E. Wasylishen, Can. J. Chem. (1980), 58, pp60-64; B. E. Cooper, Chem. Ind. (1978), pp794-797; C. A. Bruynes, T. K. Jurriens, J. Org. Chem. (1982), 47, pp3966-3969; D. N. Harpp, K. Steliou, T. H. Chan, J. Am. Chem. Soc. (1978), 100(4), pp1222-1228; and S. Berner, K. Muehlegger, H. Seliger, Nuc. Ac. Res. (1989), 17(3), pp853-864.
All of the known compositions described so far are widely regarded as effective deoxofluorination agents, but are as equally regarded as being inherently unsafe in their use because of their propensity to undergo catastrophic decomposition reactions when heated. In fact, a study, P. A. Messina, K. C. Mange, W. J. Middleton, J. Fluorine Chem. (1989), 42, pp137-143, of the thermal properties of some of the more popular of these compositions measured by differential thermal analysis (DTA) concluded that even the most stable of all compositions, 4-morpholinosulfur trifluoride, will detonate at 175.degree. C. Furthermore, in the same study, some of the even lesser stable bis(dialkylamino)sulfur difluoride derivatives were shown to be detonators at much lower temperatures than their sulfur trifluoride analogues, e.g., bis(diethylamino)sulfur difluoride detonated at 108.degree. C. while diethylaminosulfur trifluoride detonated at 147.degree. C.
The compositions of the present invention overcome the drawbacks of the prior art fluorinating agents, including DAST, by providing more thermally stable fluorine bearing compounds which have effective fluorinating capability with far less potential of violent decomposition and attendant high gaseous by-product evolvement, as will be set forth in greater detail below.